A case report and literature review: Mycobacterium leprae infection diagnosed by metagenomic next-generation sequencing of cerebrospinal fluid.
Listeria monocytogenes
Mycobacterium leprae
Case report
Leprosy
Metagenomic next-generation sequencing
Systemic lupus erythematosus
Journal
BMC infectious diseases
ISSN: 1471-2334
Titre abrégé: BMC Infect Dis
Pays: England
ID NLM: 100968551
Informations de publication
Date de publication:
03 Jul 2024
03 Jul 2024
Historique:
received:
03
03
2024
accepted:
04
06
2024
medline:
4
7
2024
pubmed:
4
7
2024
entrez:
3
7
2024
Statut:
epublish
Résumé
Leprosy is a chronic infectious disease caused by Mycobacterium leprae (M. leprae) that is responsible for deformities and irreversible peripheral nerve damage and has a broad spectrum of clinical and serological manifestations. Leprosy primarily affects the peripheral nerves and rarely presents with central nervous system involvement. Diagnosing leprosy can still be difficult in some cases, especially when the infection involves uncommon clinical manifestations and extracutaneous sites. Delayed diagnosis and treatment of leprosy may lead to irreversible damage and death. We report a case of a 30-year-old female presenting with "repeated high fever with symptoms of headache for 14 days". On the day of admission, physical signs of lost eyebrows and scattered red induration patches all over her body were observed. The patient's diagnosis was based on the clinical characteristics using a combination of metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) and slit-skin smear. After confirming Listeria meningitis and multibacillary leprosy with erythema nodosum leprosum (ENL), a type 2 reaction, she was treated with ampicillin sodium, dapsone, rifampicin, clofazimine, methylprednisolone, and thalidomide. At the 1-year follow-up, the frequency and severity of headaches have significantly decreased and a good clinical response with improved skin lesions was found. This case highlights the importance of considering leprosy, which is a rare and underrecognized disease, in the differential diagnosis of skin rashes with rheumatic manifestations, even in areas where the disease is not endemic, and physicians should be alerted about the possibility of central nervous system infections. In addition, mNGS can be used as a complementary diagnostic tool to traditional diagnostic methods to enhance the diagnostic accuracy of leprosy.
Sections du résumé
BACKGROUND
BACKGROUND
Leprosy is a chronic infectious disease caused by Mycobacterium leprae (M. leprae) that is responsible for deformities and irreversible peripheral nerve damage and has a broad spectrum of clinical and serological manifestations. Leprosy primarily affects the peripheral nerves and rarely presents with central nervous system involvement. Diagnosing leprosy can still be difficult in some cases, especially when the infection involves uncommon clinical manifestations and extracutaneous sites. Delayed diagnosis and treatment of leprosy may lead to irreversible damage and death.
CASE PRESENTATION
METHODS
We report a case of a 30-year-old female presenting with "repeated high fever with symptoms of headache for 14 days". On the day of admission, physical signs of lost eyebrows and scattered red induration patches all over her body were observed. The patient's diagnosis was based on the clinical characteristics using a combination of metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) and slit-skin smear. After confirming Listeria meningitis and multibacillary leprosy with erythema nodosum leprosum (ENL), a type 2 reaction, she was treated with ampicillin sodium, dapsone, rifampicin, clofazimine, methylprednisolone, and thalidomide. At the 1-year follow-up, the frequency and severity of headaches have significantly decreased and a good clinical response with improved skin lesions was found.
CONCLUSION
CONCLUSIONS
This case highlights the importance of considering leprosy, which is a rare and underrecognized disease, in the differential diagnosis of skin rashes with rheumatic manifestations, even in areas where the disease is not endemic, and physicians should be alerted about the possibility of central nervous system infections. In addition, mNGS can be used as a complementary diagnostic tool to traditional diagnostic methods to enhance the diagnostic accuracy of leprosy.
Identifiants
pubmed: 38961391
doi: 10.1186/s12879-024-09473-z
pii: 10.1186/s12879-024-09473-z
doi:
Substances chimiques
Leprostatic Agents
0
Types de publication
Case Reports
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
666Informations de copyright
© 2024. The Author(s).
Références
Adhe V, Dongre A, Khopkar U. A retrospective analysis of histopathology of 64 cases of lepra reactions. Indian J Dermatol. 2012;57(2):114–7.
pubmed: 22615507
pmcid: 3352632
doi: 10.4103/0019-5154.94278
Alakad R, Nofal A, Assaf M. Atypical presentations of erythema nodosum leprosum: diagnostic and therapeutic aspects. J Dtsch Dermatol Ges. 2021;19(8):1133–43.
pubmed: 34390149
Bang PD, Suzuki K, Phuong le T, Chu TM, Ishii N, Khang TH. Evaluation of polymerase chain reaction-based detection of Mycobacterium leprae for the diagnosis of leprosy. J Dermatol. 2009;36(5):269–76.
pubmed: 19382997
doi: 10.1111/j.1346-8138.2009.00637.x
Baveja S, Sandhu S, Vashisht D. A Rare Case of Possible Vacuolar Degeneration of Leprosy in Brain with Segmental Necrotizing Granulomatous Neuritis and Horner’s Syndrome. Indian Dermatol Online J. 2019;10(4):444–6.
pubmed: 31334067
pmcid: 6615378
doi: 10.4103/idoj.IDOJ_388_18
Bonomo L, Pinto L, Tursi A, Barbieri G, Dammacco F. Autoimmune reactions and macroglobulins in leprosy. Dermatol Int. 1967;6(4):214–5.
pubmed: 5302839
doi: 10.1111/j.1365-4362.1967.tb05270.x
Britton WJ, Lockwood DN. Leprosy. Lancet. 2004;363(9416):1209–19.
pubmed: 15081655
doi: 10.1016/S0140-6736(04)15952-7
Budhiraja V, Rastogi R, Khare S, Khare A, Krishna A. Histopathological changes in the arrector pili muscle of normal appearing skin in leprosy patients. Int J Infect Dis. 2010;14(Suppl 3):e70-2.
pubmed: 20207571
doi: 10.1016/j.ijid.2009.11.018
Celik O, Yalcin S, Gok U, Yavrucuoglu E, Ozturk A, Akyol A. Auditory brain stem evoked potentials in patients with leprosy. Int J Lepr Other Mycobact Dis. 1997;65(2):166–9.
pubmed: 9251587
Chao G, Fang L, Lu C. Leprosy with ANA positive mistaken for connective tissue disease. Clin Rheumatol. 2013;32(5):645–8.
pubmed: 23381668
doi: 10.1007/s10067-013-2163-0
Chauhan S, Wakhlu A, Agarwal V. Arthritis in leprosy. Rheumatology (Oxford). 2010;49(12):2237–42.
pubmed: 20724432
doi: 10.1093/rheumatology/keq264
Chiu CY, Miller SA. Clinical metagenomics. Nat Rev Genet. 2019;20(6):341–55.
pubmed: 30918369
pmcid: 6858796
doi: 10.1038/s41576-019-0113-7
Concha RM, Cossio TML, Salazar SI, Fich SF, Pérez CC. González B S. Hansen’s disease: case report and review of literature. Rev Chil Infectol. 2008;25(1):64–9.
Cuevas J, Rodríguez-Peralto JL, Carrillo R, Contreras F. Erythema Nodosum Leprosum:reactional leprosy. Semin Cutan Med Surg. 2007;26(2):126–30.
pubmed: 17544965
doi: 10.1016/j.sder.2007.02.010
Davis A, Meintjes G, Wilkinson RJ. Treatment of tuberculous meningitis and its complications in adults. Curr Treat Options Neurol. 2018;20(3):5.
pubmed: 29492737
pmcid: 5830467
doi: 10.1007/s11940-018-0490-9
de Castro RR, do Carmo FA, Martins C, Simon A, de Sousa VP, Rodrigues CR, et al. Clofazimine functionalized polymeric nanoparticles for brain delivery in the tuberculosis treatment. Int J Pharm. 2021;602:120655.
pubmed: 33915184
doi: 10.1016/j.ijpharm.2021.120655
Driedger M, Teo I, Roth V. Leprosy with type 1 reaction in a patient from Ontario, Canada without recent travel misdiagnosed as vasculitic neuropathy: a case report. BMC Infect Dis. 2023;23(1):815.
pubmed: 37990293
pmcid: 10662535
doi: 10.1186/s12879-023-08811-x
Drutz DJ, Chen TS, Lu WH. The continuous bacteremia of lepromatous leprosy. N Engl J Med. 1972;287(4):159–64.
pubmed: 4555967
doi: 10.1056/NEJM197207272870402
Ermakova N. Studies on leprosy. I. The central, sympathetic and peripheral nervous systems. Int J Lepr. 1936;4(3):325–36.
Fischer M. Leprosy - an overview of clinical features, diagnosis, and treatment. J Dtsch Dermatol Ges. 2017;15(8):801–27.
pubmed: 28763601
Griffin DE, Giffels J. Study of protein characteristics that influence entry into the cerebrospinal fluid of normal mice and mice with encephalitis. J Clin Invest. 1982;70(2):289–95.
pubmed: 7096568
pmcid: 371235
doi: 10.1172/JCI110616
Hinders DC, Taal AT, Lisam S, da Rocha AM, Banstola NL, et al. The PEP + + study protocol: a cluster-randomised controlled trial on the effectiveness of an enhanced regimen of post-exposure prophylaxis for close contacts of persons affected by leprosy to prevent disease transmission. BMC Infect Dis. 2024;24(1):226.
pubmed: 38378497
pmcid: 10877766
doi: 10.1186/s12879-024-09125-2
Job CK, Yoder L, Jacobson RR, Hastings RC. Skin pigmentation from clofazimine therapy in leprosy patients: a reappraisal. J Am Acad Dermatol. 1990;23(2 Pt 1):236–41.
pubmed: 2145325
doi: 10.1016/0190-9622(90)70204-U
Kamath S, Vaccaro SA, Rea TH, Ochoa MT. Recognizing and managing the immunologic reactions in leprosy. J Am Acad Dermatol. 2014;71(4):795–803.
pubmed: 24767732
doi: 10.1016/j.jaad.2014.03.034
Karadeniz A, Lally L, Magro C, Levy R, Erkan D, Lockshin MD. Lepromatous Leprosy mimicking systemic lupus erythematosus: a clinical pathology conference held by the division of rheumatology at hospital for special surgery. HSS J. 2014;10(3):286–91.
pubmed: 25264448
pmcid: 4171453
doi: 10.1007/s11420-014-9405-9
Khadilkar SV, Kasegaonkar PS, Ursekar M. Spinal cord involvement and ganglionitis in leprosy. Neurol India. 2007;55(4):427–8.
pubmed: 18040133
doi: 10.4103/0028-3886.33312
Kumar S, Alexander M, Gnanamuthu C. Cranial nerve involvement in patients with leprous neuropathy. Neurol India. 2006;54(3):283–5.
pubmed: 16936390
doi: 10.4103/0028-3886.27154
Li M, Yan K, Jia P, Wei E, Wang H. Metagenomic next-generation sequencing may assist diagnosis of cat-scratch disease. Front Cell Infect Microbiol. 2022;12:946849.
pubmed: 36189365
pmcid: 9524480
doi: 10.3389/fcimb.2022.946849
Lumsden CE. Leprosy and the Schwann cell in vivo and in vitro. In: Cochrane RG, Davey TF, editors. Leprosy in Theory and Practice. 2nd ed. Baltimore: Williams and Wilkins; 1964. p. 221–50.
Polavarapu K, Preethish-Kumar V, Vengalil S, Nashi S, Lavania M, Bhattacharya K, et al. Brain and Spinal Cord Lesions in Leprosy: a magnetic resonance imaging-based study. Am J Trop Med Hyg. 2019;100(4):921–31.
pubmed: 30761984
pmcid: 6447108
doi: 10.4269/ajtmh.17-0945
Quagliarello VJ, Long WJ, Scheld WM. Morphologic alterations of the blood-brain barrier with experimental meningitis in the rat. Temporal sequence and role of encapsulation. J Clin Invest. 1986;77(4):1084–95.
pubmed: 3514671
pmcid: 424442
doi: 10.1172/JCI112407
Quan M, Liu L, Zhou T, Jiang Y, Wang X, Zong Z. Leprosy in a low-incidence setting: case report relevant to metagenomic next generation sequencing applications. Wien Klin Wochenschr. 2020;132(19–20):589–92.
pubmed: 32291523
doi: 10.1007/s00508-020-01644-7
Ribeiro SL, Pereira HL, Silva NP, Neves RM, Sato EI. Anti-cyclic citrullinated peptide antibodies and rheumatoid factor in leprosy patients with articular involvement. Braz J Med Biol Res. 2008;41(11):1005–10.
pubmed: 19099154
doi: 10.1590/S0100-879X2008001100010
Sampaio LH, Stefani MM, Oliveira RM, Sousa AL, Ireton GC, Reed SG, et al. Immunologically reactive M. Leprae antigens with relevance to diagnosis and vaccine development. BMC Infect Dis. 2011;11:26.
pubmed: 21269435
pmcid: 3040138
doi: 10.1186/1471-2334-11-26
Sharma R, Singh P, McCoy RC, Lenz SM, Donovan K, Ochoa MT, et al. Isolation of Mycobacterium lepromatosis and development of molecular diagnostic assays to Distinguish Mycobacterium leprae and M. lepromatosis. Clin Infect Dis. 2020;71(8):e262-9.
pubmed: 31732729
doi: 10.1093/cid/ciz1121
Shi J, Yang N, Qian G. Case Report: Metagenomic Next-Generation sequencing in diagnosis of talaromycosis of an Immunocompetent patient. Front Med (Lausanne). 2021;8:656194.
pubmed: 33855039
doi: 10.3389/fmed.2021.656194
Smith CS, Aerts A, Saunderson P, Kawuma J, Kita E, Virmond M. Multidrug therapy for leprosy: a game changer on the path to elimination. Lancet Infect Dis. 2017;17(9):e293-7.
pubmed: 28693853
doi: 10.1016/S1473-3099(17)30418-8
Suzuki K, Udono T, Fujisawa M, Tanigawa K, Idani G, Ishii N. Infection during infancy and long incubation period of leprosy suggested in a case of a chimpanzee used for medical research. J Clin Microbiol. 2010;48(9):3432–4.
pubmed: 20631101
pmcid: 2937736
doi: 10.1128/JCM.00017-10
Vaidya MC, Palmer E, Weddell G, Rees RJ. A note on the presence of Mycobacterium leprae in the central nervous system of a mouse with lepromatous leprosy. J Med Microbiol. 1970;3(1):194–6.
pubmed: 4915372
doi: 10.1099/00222615-3-1-194
Verma S, Garg RK, Rizvi I, Malhotra HS, Kumar N, Jain A, et al. Central nervous system, spinal root ganglion and brachial plexus involvement in leprosy: a prospective study. J Cent Nerv Syst Dis. 2022;14:11795735221135476.
pubmed: 36277272
pmcid: 9583215
doi: 10.1177/11795735221135477
Voorend CG, Post EB. A systematic review on the epidemiological data of erythema nodosum leprosum, a type 2 leprosy reaction. PLoS Negl Trop Dis. 2013;7(10):e2440.
pubmed: 24098819
pmcid: 3789767
doi: 10.1371/journal.pntd.0002440
Walker SL, Waters MF, Lockwood DN. The role of thalidomide in the management of erythema nodosum leprosum. Lepr Rev. 2007;78(3):197–215.
pubmed: 18035771
doi: 10.47276/lr.78.3.197
White C, Franco-Paredes C. Leprosy in the 21st century. Clin Microbiol Rev. 2015;28(1):80–94.
pubmed: 25567223
pmcid: 4284303
doi: 10.1128/CMR.00079-13
Wilson MR, Sample HA, Zorn KC, Arevalo S, Yu G, Neuhaus J, et al. Clinical metagenomic sequencing for diagnosis of Meningitis and Encephalitis. N Engl J Med. 2019;380(24):2327–40.
pubmed: 31189036
pmcid: 6764751
doi: 10.1056/NEJMoa1803396
Woldemichael B, Molla M, Aronowitz P. Erythema Nodosum Leprosum. J Gen Intern Med. 2021;36(5):1429–30.
pubmed: 33515194
pmcid: 8131450
doi: 10.1007/s11606-021-06620-z
Xing XW, Yu SF, Zhang JT, Tan RS, Ma YB, Tian X, et al. Metagenomic next-generation sequencing of Cerebrospinal Fluid for the diagnosis of cerebral aspergillosis. Front Microbiol. 2021;12:787863.
pubmed: 35003020
pmcid: 8740169
doi: 10.3389/fmicb.2021.787863
Zavala-Cerna MG, Fafutis-Morris M, Guillen-Vargas C, Salazar-Páramo M, García-Cruz DE, Riebeling C, et al. Anti-cyclic citrullinated peptide antibodies and rheumatoid factor sera titers in leprosy patients from Mexico. Rheumatol Int. 2012;32(11):3531–6.
pubmed: 22083616
doi: 10.1007/s00296-011-2224-0
Zhang P, Zhang ZH, Liang J, Shen DY, Li J, Wang D, et al. Metagenomic next-generation sequencing for the diagnosis of fever of unknown origin in pediatric patients with hematological malignancy. Clin Chim Acta. 2022;537:133–9.
pubmed: 36283493
doi: 10.1016/j.cca.2022.10.008